title: Anti-tumor activity and immunogenicity of a mutated staphylococcal enterotoxin C2.
abstract: In this study, a novel SEC2 mutant with lower toxic activity, named 2M-118 (H118A/T20L/G22E), was engineered by site-directed mutagenesis of structural domains that are responsible for MHC class II molecule binding and TCR binding, respectively. Stimulating activity on murine splenocytes, anti-tumor effect and immunogenicity of 2M-118 were investigated in BALB/c mice. 2M-118 not only remained splenocyte stimulation activity, but also effectively inhibited the growth of S180 sarcoma in the BALB/c mice. Even though antibodies to 2M-118 could be induced after repeated administration, the action of 2M-118 was hardly neutralized or cross neutralized. Like other superantigens, immunosuppression could happen when 2M-118 was given at a greater dose. In conclusion, 2M-118 is a promising anti-tumor drug candidate for its acceptable toxicity and satisfying anti-tumour efficacy.
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: Y M
authors.initials: YM
authors.lastname: Cai
authors.forename: M K
authors.initials: MK
authors.lastname: Xu
authors.forename: Z H
authors.initials: ZH
authors.lastname: Song
authors.forename: C Y
authors.initials: CY
authors.lastname: Li
authors.forename: H R
authors.initials: HR
authors.lastname: Wang
authors.forename: H H
authors.initials: HH
authors.lastname: Dai
authors.forename: Z P
authors.initials: ZP
authors.lastname: Zhang
authors.forename: C X
authors.initials: CX
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004768:Enterotoxins / Q000276:immunology* / Q000494:pharmacology* / Q000633:toxicity; D004797:Enzyme-Linked Immunosorbent Assay; D005802:Genes, MHC Class II / Q000235:genetics; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D016297:Mutagenesis, Site-Directed; D010957:Plasmids / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D004768:Enterotoxins; D011948:Receptors, Antigen, T-Cell; C034959:enterotoxin C, staphylococcal